More Like this

1. Model reduction and stochastic analysis of the histone modification circuit

   https://doi.org/10.23919/ECC55457.2022.9838047  

   Bruno, Simone ; Williams, Ruth J. ; Del Vecchio, Domitilla ( July 2022 , IEEE European Control Conference)

   Epigenetic cell memory (ECM), the inheritance of gene expression patterns without changes in genetic sequence, is a critical property of multi-cellular organisms. Chromatin state, as dictated by histone covalent modifications, has recently appeared as a mediator of ECM. In this paper, we conduct a stochastic analysis of the histone modification circuit that controls chromatin state to determine key biological parameters that affect ECM. Specifically, we derive a one-dimensional Markov chain model of the circuit and analytically evaluate both the stationary probability distribution of chromatin state and the mean time to switch between active and repressed chromatin states. We then validate our analytical findings using stochastic simulations of the original higher dimensional circuit reaction model. Our analysis shows that as the speed of basal decay of histone modifications decreases compared to the speed of autocatalysis, the stationary probability distribution becomes bimodal and increasingly concentrated about the active and repressed chromatin states. Accordingly, the switching time between active and repressed chromatin states becomes larger. These results indicate that time scale separation among key constituent processes of the histone modification circuit controls ECM.
2. Chromatin assembly: Journey to the CENter of the chromosome

   https://doi.org/10.1083/jcb.201605005  

   Chen, Chin-Chi ; Mellone, Barbara G. ( July 2016 , The Journal of Cell Biology)

   All eukaryotic genomes are packaged into basic units of DNA wrapped around histone proteins called nucleosomes. The ability of histones to specify a variety of epigenetic states at defined chromatin domains is essential for cell survival. The most distinctive type of chromatin is found at centromeres, which are marked by the centromere-specific histone H3 variant CENP-A. Many of the factors that regulate CENP-A chromatin have been identified; however, our understanding of the mechanisms of centromeric nucleosome assembly, maintenance, and reorganization remains limited. This review discusses recent insights into these processes and draws parallels between centromeric and noncentromeric chromatin assembly mechanisms.
3. Model reduction and stochastic analysis of the histone modification circuit

   Simone Bruno, Ruth J. ( July 2022 , European Control Conference)

   Epigenetic cell memory (ECM),the inheritance of gene expression patterns without changes in genetic sequence,is acritical property of multi-cellular organisms.Chromatin state, as dictated by histone covalent modifications, has recently appeared as a mediator of ECM. In this paper,we conduct a stochastic analysis of the histone modification circuit that controls chromatin state to determine key biological parameters that affect ECM. Specifically, we derive a one-dimensional Markov chain model of the circuit and analytically evaluate both the stationary probability distribution of chromatin state and the mean time to switch between active and repressed chromatin states.We then validate our analytical findings using stochastic simulations of the original higher dimen- sional circuit reaction model.Our analysis shows that as the speed of basal decay of histone modifications decreases compared to the speed of autocatalysis,the stationary probability distribution becomes bimodal and increasingly concentrated about the active and repressed chromatin states. Accordingly, the switching time between active and repressed chromatin states becomes larger.These results indicate that timescale separation among key constituent processes of the histone modification circuit controls ECM.
4. Epigenetic cell memory: The gene’s inner chromatin modification circuit

   https://doi.org/10.1371/journal.pcbi.1009961  

   Bruno, Simone ; Williams, Ruth J. ; Del Vecchio, Domitilla ( April 2022 , PLOS Computational Biology)

   Herrmann, Carl (Ed.)

   Epigenetic cell memory allows distinct gene expression patterns to persist in different cell types despite a common genotype. Although different patterns can be maintained by the concerted action of transcription factors (TFs), it was proposed that long-term persistence hinges on chromatin state. Here, we study how the dynamics of chromatin state affect memory, and focus on a biologically motivated circuit motif, among histones and DNA modifications, that mediates the action of TFs on gene expression. Memory arises from time-scale separation among three circuit’s constituent processes: basal erasure, auto and cross-catalysis, and recruited erasure of modifications. When the two latter processes are sufficiently faster than the former, the circuit exhibits bistability and hysteresis, allowing active and repressed gene states to coexist and persist after TF stimulus removal. The duration of memory is stochastic with a mean value that increases as time-scale separation increases, but more so for the repressed state. This asymmetry stems from the cross-catalysis between repressive histone modifications and DNA methylation and is enhanced by the relatively slower decay rate of the latter. Nevertheless, TF-mediated positive autoregulation can rebalance this asymmetry and even confers robustness of active states to repressive stimuli. More generally, by wiring positively autoregulated chromatin modificationmore »circuits under time scale separation, long-term distinct gene expression patterns arise, which are also robust to failure in the regulatory links.« less
5. Histone Variants in the Specialization of Plant Chromatin

   https://doi.org/10.1146/annurev-arplant-070221-050044  

   Foroozani, Maryam ; Holder, Dylan H. ; Deal, Roger B. ( May 2022 , Annual Review of Plant Biology)

   The basic unit of chromatin, the nucleosome, is an octamer of four core histone proteins (H2A, H2B, H3, and H4) and serves as a fundamental regulatory unit in all DNA-templated processes. The majority of nucleosome assembly occurs during DNA replication when these core histones are produced en masse to accommodate the nascent genome. In addition, there are a number of nonallelic sequence variants of H2A and H3 in particular, known as histone variants, that can be incorporated into nucleosomes in a targeted and replication-independent manner. By virtue of their sequence divergence from the replication-coupled histones, these histone variants can impart unique properties onto the nucleosomes they occupy and thereby influence transcription and epigenetic states, DNA repair, chromosome segregation, and other nuclear processes in ways that profoundly affect plant biology. In this review, we discuss the evolutionary origins of these variants in plants, their known roles in chromatin, and their impacts on plant development and stress responses. We focus on the individual and combined roles of histone variants in transcriptional regulation within euchromatic and heterochromatic genome regions. Finally, we highlight gaps in our understanding of plant variants at the molecular, cellular, and organismal levels, and we propose new directions for studymore »in the field of plant histone variants.« less